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The Impact of HIV-1 Infection on NK Cell Phenotypes and Non-classical Helper Functions

Bronson, Rhianna (2022) The Impact of HIV-1 Infection on NK Cell Phenotypes and Non-classical Helper Functions. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Although treatment with antiretroviral therapy (ART) results in HIV viral suppression to undetectable viral loads, systemic inflammation continues to persist over long-term administration of ART. Exactly how this state of chronic inflammation affects NK cell phenotypes and their non-classical helper functionality remains to be fully determined. Here we report that a subpopulation of CD56dim NK cells lacking FcRγ (FcRγ-), which are deficient in providing immune help in response to innate stimuli, are highly expanded in the peripheral blood of HIV+ individuals as far out as four years on ART. Surface and intracellular staining, followed by quantification through flow cytometry, identified phenotypic and functional differences of FcRγ- NK cells and revealed that these differences do not return to conventional baselines over time. Since this helper deficient FcRγ- NK cell phenotype accumulates in the periphery of people living with HIV (PLWH), we hypothesize that this may translate into a decreased capacity among PLWH to generate effective primary adaptive immune responses elicited by the novel COVID-19 vaccines. Therefore, we performed a detailed characterization of peripheral blood NK cell and T cell phenotypes in PLWH at time points before and after COVID-19 vaccination as part of a larger multi-research group HIV project. These data will be included along with vaccine induced antibody responses, cellular responses, and HIV reservoir data as part of a multiparameter machine learning approach to determine the overall impact(s) of HIV infection and NK cell subset distribution on COVID-19 vaccine outcomes. Our initial results suggest that an increased percentage of FcRγ- peripheral blood NK cells is associated with lower vaccine-induced antigen-specific T cell responses to the SARS-CoV-2 spike protein in overnight and 10-day cultures. Determining the effect of HIV infection on COVID-19 vaccination responses in individuals on ART, provides important insight into the immunocompromised state of PLWH and how this may affect vaccine efficacy, leading to future changes in immunization recommendations in the HIV+ population.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Bronson, Rhiannarhb31@pitt.edurhb31
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorMailliard, Robbierbm19@pitt.edurbm19
Committee MemberBoth, Camilacpm13@pitt.educpm13
Committee MemberMarques, Ernesto Torres De Azevedmarques@pitt.edumarques
Date: 10 May 2022
Date Type: Publication
Defense Date: 26 April 2022
Approval Date: 10 May 2022
Submission Date: 28 April 2022
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 50
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: NK cells, COVID-19, FcRy-, FcRg-, NK, T-cell, Phenotype, Function, HIV, ART, vaccination, IFNy, IFNg, antigen-specific, FcRy, FcRg
Date Deposited: 10 May 2022 20:07
Last Modified: 10 May 2022 20:07
URI: http://d-scholarship.pitt.edu/id/eprint/42866

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